This is part of a continuing project to study the role of electrolytes in the storage, uptake and release of biogenic amines in nerve endings. According to previous reports norepinephrine is thought to be mobilized by a calcium dependent mechanism that is regulated by intracellular sodium. The efflux is mediated by a sodium-facilitated mechanism that can be inhibited by desipramine, suggesting the involvement of transport. For the studies reported below, apparent outward transport of tritiated norepinephrine (H3-NE) in sympathetic nerve endings was studied in rat heart slices incubated in a sodium-deficient medium (choline ion). Both efflux and uptake were inhibited by cocaine, desipramine and phenoxybenzamine. The ID50 for each drug is approximately equal for both effects. Extracellular NE exchanges with intracellular NE and the exchange is mediated by two mechanisms having apparent Km values of 0.14 and 1.3 micron M. Ouabain is a good inhibitor of uptake but it is a poor inhibitor of efflux. It is concluded that transport is mediated by one or more mechanisms and that the mechanisms for uptake and efflux are similar or identical. If so, ouabain inhibits transport indirectly, unlike the other inhibitors. These conclusions support the sodium-gradient hypothesis of transport.